Foamed lozenge containing grafted copolymer of polyvinyl alcohol and polyethylene glycol

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention related to chemical-pharmaceutical and cosmetic industry, and deals with lamellar form of delivery, dissolving or decomposing in water medium, for release of, at least, one medicinal or cosmetically acting substance into hole or cavity in body, including polymer matrix in form of hardened foam with spaces or cavities, as well as, at least, one medicinal or cosmetic active substance, characterised by the fact, that matrix polymer is represented by grafted copolymer of polyvinyl alcohol and polyethylene glycol, which consists on 75% from polyvinyl alcohol and on 25% from polyethylene glycol. Also described are methods of said medicinal forms manufacturing.

EFFECT: elaboration of lamellar form of medication delivery.

6 cl, 2 ex

 

For the introduction of active substances through the mucous membrane of the oral cavity usually use tablets for slow dissolution in the buccal pocket or sublingual tablets, releasing the active ingredient into the oral cavity. Compared with other dosage forms, the absorption of the active substance through the mucous membrane of the mouth is preferred since it allows you to enter medication by mouth, for example, even patients with difficulty swallowing, provides rapid onset of action due to the passage bypassing the intestines and high utilization of the active substance.

Alternatively known dosage forms as tablets for slow dissolution in the buccal pocket or sublingual tablets are used lamellar dosage forms, called "lozenges".

In U.S. patent 5529782 described instant device from soluble polymeric material or a complex of polysaccharides, mainly for the introduction of contraceptives. This device must have a thickness of from 3 to 4.5 mm and adjustable solubility to dissolved within 5 to 60 seconds after injection. It is understood that this device must also have a layered form with cavities created by foaming with gas.

In the application WO 98/26764 described containing the active substance film dosage form that dissolves quickly upon contact with the fluid and in which the fat-soluble phase is distributed in the form of liquid droplets in the outer water-soluble phase.

In the application WO 00/18365 described food film with rapid solubility, but also able well to stick to the mucosa of the oral cavity for delivery of antimicrobial agents and reduce the number of undesirable microorganisms in the oral Flor is. These antimicrobial agents are essential oils, mixed with the aqueous phase in the form of a lipophilic phase, preferably containing pullulan as matrix material.

In the patent application U.S. 2001/006677 described film effervescent and soluble in water or swellable in water dosage forms, easily adhering to the mucous membrane of the mouth.

In the application WO 02/02085 described rapidly disintegrating dosage form for the release of active substances in the oral cavity or other openings in the body, including the matrix, which contains at least one water-soluble polymer as a matter of basics and has a cavity.

In the application WO 2004/060298 described soluble film for oral administration of medicinal active substances, comprising a graft copolymer of polyvinyl alcohol and polyethylene glycol and the active substance.

In the application WO 2005/009386 described instant film, which can be used for oral administration of a cosmetic or pharmaceutical active substances. The basis of these films is a graft copolymer of polyvinyl alcohol and polyethylene glycol.

Due to lamellar shape and smooth surface known mints tend to stick and firmly stick to the sky or other surfaces of the mucous membranes of the oral cavity, even if they are not conceived as adherent to the mucous membrane of the dosage form. This negative property is especially true for relatively thick pastilles, because the disintegration time of tablets depends, inter alia, from its thickness, and thicker tablets disintegrate more slowly than thin mints. As a consequence, especially in the case of relatively thick pastilles, it is very important perception sticky polipovidnami film formed from the dissolving of the outer layers of the polymer.

When the toffee sticks and firmly adheres to the mucous membranes of the oral cavity, the oral cavity occurs unpleasant and irritating sensation, which is called "taste". To improve the sensations caused by toffee, in the application WO 02/02085 proposed lamellar dosage form, rapidly disintegrating or fast rastvoryayas in the aquatic environment and having a space or cavity inside the polymer matrix mentioned dosage forms, the content of which differs from that of the matrix from the point of view of the aggregate state.

However, as the test showed a smack lamellar dosage form proposed in WO 02/02085 also requires improvement to ensure that no unpleasant or irritating sensation in the mouth when taking this form of drug, even those with high sensitivity.

Thus, the object of the invention is the creation of a lamellar drugs the military form of a hardened foam, rapidly disintegrating or rapidly dissolving in water and quickly releasing at least one pharmaceutical or cosmetic active substance in the holes or cavities of the body, preferably the oral cavity without causing unpleasant or irritating sensation in the mouth after taking the mentioned dosage forms.

Another disadvantage of dosage forms, known as lozenges or hardened foam is requiring a large expenditure of time and energy in their production process. So, according to known methods for the production of partially saponified polyvinyl alcohol is usually dissolved in water with temperatures ranging from 80 to 90°C. This process takes approximately 2-3 hours. In addition, you need a long-term or active cooling solution until it is foaming.

Therefore, another objective of the present invention is to provide a method for manufacturing the plate of the dosage form in the form of a hardened foam, rapidly disintegrating or rapidly dissolving in water, for the release of active substances into the holes in the body, which overcome or at least weakened the disadvantages of the known manufacturing methods in terms of energy cost and/or time consuming process.

Surprisingly, the aforementioned task is solved by the plate of the dosage form with polim the nuclear biological chemical (NBC matrix in the form of a hardened foam of the grafted copolymer of polyvinyl alcohol and polyethylene glycol and by the way, in order to obtain the hardened foam for the manufacture of the mentioned plate pharmaceutical form containing at least one active ingredient, use of grafted copolymer of polyvinyl alcohol and polyethylene glycol.

Proposed in the present invention, the dosage form is a lamellar dosage form, disintegrating or dissolving in an aqueous environment to release at least one active substance in a hole or cavity in the body, these lamellar dosage form comprises a matrix in the form of a hardened foam with spaces or cavities, and at least one pharmaceutical or cosmetic active ingredient. As proposed in the present invention the dosage form mentioned space or cavity in the foam filled with gas, mixture of gases, liquid or mixture of liquids. Proposed invention, the dosage form is characterized by the fact that, as the polymer matrix using grafted copolymer of polyvinyl alcohol and polyethylene glycol.

The preferred graft copolymer of polyvinyl alcohol and polyethylene glycol is a graft copolymer of polyvinyl alcohol and polyethylene glycol, having the trade name Kollicoat®IR (BASF AG, Ludwigshafen), consisting of 75% polivi the silt alcohol and 25% peg.

Kollicoat®IR is a water-soluble polymer that can be applied as a coating of tablets or as a film-forming substance in spray materials and transdermal therapeutic systems.

Space or cavity in a polymer matrix dosage form according to the invention can be isolated from each other and preferably have the form of hardened bubbles.

In another embodiment, the space or cavity are connected to each other and preferably form a system of interconnecting channels passing through the matrix.

The proportion of the spaces or cavities varies from 5 to 98%, preferably 50-80% of the total dosage form.

Space or cavity is preferably filled with a gas or gas mixture, more preferably air. However, the space or cavity may contain other gases or gas mixtures. Space/cavity is preferably filled with inert gas, i.e. a gas or mixture of gases, not reacts with other components of the dosage form. Particularly preferred gases are nitrogen, carbon dioxide and helium, and a mixture of these gases or two of these gases.

In another embodiment, the space or cavity filled with liquid or mixture of liquids (e.g. oil), mentioned the liquids are not mixed with the matrix material and does not dissolve the polymer frame matrix. In addition, the liquid or mixture of liquids may contain one or more pharmaceutical and/or cosmetic active ingredients.

As proposed in the present invention, the dosage form is in the form of a dry foam, the intended effect of reducing adhesion is achieved without unduly limiting the ability of the dosage form to absorb the active ingredient.

Other important parameters that affect the properties of the proposed invention the dosage form is the diameter of the cavities or bubbles. Bubbles or cavities are preferably produced using the equipment for production of foamed material. Due to this, the diameter of bubbles can almost arbitrarily be adjusted in a wide range. Thus, the diameter of bubbles or cavities may be from 0.01 to 50 μm, are preferred vesicles/cavities having a diameter of from 0.1 to 10 μm.

In the simplest embodiment, the cavity of the proposed invention the dosage form does not contain the active substance. However, the space or cavity predominantly contain active substances, excipients and/or additives to achieve certain effects. Particularly preferred substances that may be contained in the spaces/cavities, are surface-active substances or g is soobrazayuschie substances, with the help of which you can speed up the disintegration of the dosage form after its application.

In addition, with the purpose of further weakening trends adhesion of dosage forms for mucosal surfaces of the dosage form can be given the unevenness or irregularity, preferably waviness or relief, or they can be structured. The surface can be given an irregular structure, for example, with the help of cavities in the form of bubbles, which are introduced in the polymer matrix, and/or by subsequent special treatment drying.

Proposed in the present invention dosage forms are, for example, thin mints. The thickness of the dosage form is preferably from 0.1 to 5 mm, more preferably from 0.5 to 1 mm. Minimum thickness of the dosage form is about 50 µm.

Applicable active substances include, without limitation has a therapeutic effect connection. They can belong to various groups, including means for treatment of infections; vironostika means; analgesics such as fentanyl, Sufentanil, buprenorphine; anaesthetics; anorectics; active substances for the treatment of arthritis and asthma, such as terbutaline; anticonvulsants; antidepressants; protivodiabeticski the e means; antihistaminics means; Antidiarrhoeal tools; anti-migraines, itching, nausea and vomiting, motion sickness in transport or sea sickness, such as scopolamine and ondansetron; ANTIPARKINSONISM funds; antipsychotics; antipyretics; antispasmodic; anticholinergic agents; anti-ulcer, such as ranitidine; sympathomimetic means; calcium channel blockers such as nifedipine; beta blockers; beta-agonists such as dobutamine; antiarrhythmic means; protivogipertonicheskoe tools, such as atenolol; inhibitors of the angiotensin converting enzyme (ACE), such as enalapril; agonists of benzodiazepine such as flumazenil; means for expanding coronary, peripheral and cerebral vessels; Central nervous system stimulants; hormones; hypnotics means; immunosuppressive means; muscle relaxants; parasympatholytics means; parasympathomimetics means; prostaglandins; proteins; peptides; psychostimulants; sedatives; tranquilizers.

For use in the mouth or on the mucous membrane of the mouth is applicable to virtually all active substances that can be absorbed transbukkalno and/or through the gastrointestinal tract.

Particularly preferred acting the substance is nicotine. Nicotine can be applied not only in the form of the free bases but also in the form of one or more of its pharmaceutically acceptable salts. Pharmaceutically acceptable salts of nicotine are, for example, nicotinate, nicotinamidase, nicotinamidase, nicotinuric, double salt nicotinamidase zinc, natinalities. Similarly, a potential source of nicotine is polacrilin.

The content of active substance in the standard dose is 50 mg, preferably up to 30 mg, more preferably up to 20 mg

Additional substances used as active ingredients and/or auxiliary substances, are:

polishing agent tools, grinding compounds (abrasive), such as titanium dioxide, silicon dioxide, etc.; sodium fluoride, dicalcium phosphate, essential oils such as anise oil, vangeluwe oil, eucalyptus oil, peppermint oil, peppermint oil, curly, orange oil, oil of Dalmatian sage, thyme oil, lemon oil, etc.; flavouring substances, such as camphor, cineole, eucalyptol, menthol, pinene, cinnamic aldehyde, cinnamic acid, etc., honey, citric acid, vitamins, oxidation inhibitors, sorbitol.

Thus, the proposed in the present invention the dosage form is also applicable in Cosme what practical purposes, as well as in the field of dental care, teeth cleaning, oral hygiene or dental hygiene.

In addition, the dosage form as flavouring substances separately or in combination can contain the following ingredients: vanilla flavoring, orange flavoring, cream and orange flavoring, strawberry flavoring, raspberry flavoring or chocolate flavoring. In addition, there may be added one or more sweeteners, for example, Sucralose, aspartame, cyclamate, saccharin and Acesulfame, as well as their salts.

Applicable supporting means, among others, well known to experts in the art, are substances from the following groups:

carboxymethylcellulose, gum Arabic, methylcellulose, pectin, modified and unmodified starches, gelatin, animal and/or vegetable protein, egg albumin, alginates, Bridge or Brij (emulsifier), isopropanol, benzyl alcohol, ethyl acetate, utiltity, octisalate, 1,2-propylenglycol, magnesium stearate, stearic acid, microcrystalline cellulose, Aerosil, lecithin, twin, propylgallate, AMILOcam.

In addition, the foam can be dissolved sugar or mixture of sugars) or at least one other carbohydrate. Sugar or other carbohydrate increases the mass of the foam after drying. In addition, as a result of drying and crystal is the form of sugar or other carbohydrate dry foam acquires additional strength and stability. Sugar or other carbohydrates can give dry foam sweet taste or otherwise improve the organoleptic properties of the foam. Examples of sugars that may be contained in the dosage form are maltose, lactose, sucrose, dextrose (glucose) and trehalose. Also applicable alcohols on the basis of sugar, such as mannitol, sorbitol, xylitol, ▫ maltitol and the like, Examples of other applicable hydrocarbons are maltodextrins, syrup dextrose (from corn), soluble starches, etc.

Although the proposed invention, the dosage form is designed, in particular, for oral administration, its application is not limited to the introduction of active substances in the field of the oral cavity. In the scope of the present invention also include dosage forms, which are injected into the other cavities or holes in the body, in which they release the contained active substances. Examples, which should lead in this regard, are rectal, vaginal or intranasal dosage form.

The active substance is released from the dosage form, absorbed in the place of use, for example, through the mucous membrane of the mouth or carried forward and sucked in another place (for example, in the gastrointestinal tract after ingestion of the active substance released in the mouth).

The offer is fair to the invention, the dosage form is a drug, which quickly disintegrates or dissolves in aqueous media. The time of retention of the proposed invention the dosage form at the site of application (e.g., oral) or its disintegration time is preferably from 1 sec. to 5 min, more preferably from 5 s to 1 min, and most preferably from 10 to 30 C.

In addition, in the manufacturing process proposed in the invention, the dosage forms can be added one or more acids to give the foam a pleasant sour taste. Examples of such acids are citric acid, lactic acid, acetic acid, benzoic acid, propionic acid, oxalic acid, malonic acid, succinic acid, maleic acid and tartaric acid. Adding acid or acids may also be necessary or desirable to reduce the pH of the foam. This is particularly desirable in those cases where the active ingredient contained in the dosage form relatively insoluble in an alkaline environment, such as ibuprofen, or when the active substance is unstable in an alkaline environment.

In addition, as proposed in the present invention the dosage form can be added to the wetting or moistening means to improve the aesthetic properties of dry foam and reduce brittleness or fragility dry foam. Examples of such substances are glits is Rin, propylene glycol and complex polyglyceryl ether. In addition, before or after drying may be added a surfactant to improve the stability of the foam before or after drying. Examples of applicable surface-active substances are, in particular, substituted derivatives sorbitan, preferably group "tween" (ICI).

The manufacturing methods

Known methods of manufacturing the plate of dosage forms in the form of a hardened foam require a large expenditure of time and energy, because the process temperature for the dissolution of partially saponified polyvinyl alcohol in water until foaming is usually 80-90°C, and saponified polyvinyl alcohol should be dissolved at this temperature by stirring for 2-3 hours. Before foaming the resulting solution must be cooled by prolonged or active cooling.

Thus, another objective of the present invention is to provide a method for manufacturing the plate of dosage forms, rapidly disintegrating or dissolving in aqueous media, which overcome the above-mentioned disadvantages.

Through the use of grafted copolymer of polyvinyl alcohol and polyethylene glycol manufacturer proposed invention the dosage form can be carried out at room tempera is ur except for the drying of foamed solution. The dissolution of the graft copolymer of polyvinyl alcohol and polyethylene glycol in water at room temperature is advantageous from the point of view of energy and time consuming process compared to the known methods, in which the polymer or mixture of polymers is dissolved at higher temperatures. In addition, the proposed invention the method is also advantageous from the viewpoint of stability of the active substance, in particular, when the active substance is added to the solvent to the polymer.

For manufacturing of the proposed invention dosage forms with improved "flavor" offers the following methods.

In a particularly preferred method of manufacturing first get a solution or dispersion containing a graft copolymer of polyvinyl alcohol and polyethylene glycol, and at least one active substance. Then, this solution, which can also be a concentrated solution or viscous mass, foamed by introducing a gas or mixture of gases (e.g. air). This can be done by using a dispersing device or unit for production of foamed material, but also in other ways, for example, using ultrasound. Applicable gases include inert gases such as nitrogen, carbon dioxide or helium, or a mixture of inert gas the century

For stabilization obtained in this way pins or containing air bubbles or gas bubbles) mass before or during foaming can be added foam stabilizer. Tools applicable for this purpose, for example, surface-active substances known to specialists in this field of technology. Finally, containing bubbles of air mass or foam in the form of a film or layer applied to the appropriate substrate and then dried. Since the solvent is removed, the foam hardens during drying to form the aerogel, thus formed cavity acquire a permanent structure.

To obtain tablets with the desired dimensions of the surface or geometric shapes foamed coating mass is poured into the forms, or to carve or cut out a separate plate from a piece with a larger surface area.

Produced in this way contains the active substance pharmaceutical form have properties and advantages of the present invention, which means that they quickly disintegrate after oral administration without causing discomfort on the mucous membrane of the mouth.

On the form, the number and sizes of the formed spaces or cavities can be influenced by various process parameters, such as concentration of the grafted copolymer of polyvinyl alcohol and is of etilenglikola, the viscosity of the polymer mass, regulation foaming process or selection of foam stabilizers.

For the manufacture of a particularly preferred dosage forms intended for the introduction of nicotine, it is necessary to ensure the absence of nicotine in the foam solution in the form of a Foundation, but not the salt that nicotine does not evaporate during the subsequent drying of the foam. To this end, the nicotine can be introduced into the polymer solution in the form of one of the pharmaceutically acceptable salts, e.g. in the form of nicotinate. Alternatively, nicotine may be introduced into the polymer solution and then in a molar ratio of 1.4:1 relative to nicotine can be added to fruit acid, preferably fruit acid, applicable in food, which can also serve as a substance that corrects the taste of the medicine. Thereby, there is formed the corresponding nicotine salt, and prevents evaporation of nicotine during the drying of the foam. Nicotine base would evaporate during the drying temperature 80°C, which is not the case with salt.

For the formation of a nicotine salt is applicable to all fruit acids, but preferably use citric acid or dicarboxylic acid, in particular, maleic acid, succinic acid, fumaric acid and tartaric acid. Can also be used mixtures of the corresponding FR is kitovich acids.

In another method of manufacture of dosage forms according to the invention as an improvement of the above-described method of space or cavity inside the polymer matrix is formed by introducing a hydrophobic solvent which is not miscible with the solvent used to obtain the above-mentioned solution or dispersion.

Due to this emulsion is formed containing a hydrophobic solvent in the form of well-dispersed fine droplets. Due to the removal of the solvent in the subsequent drying in a polymeric matrix remains cavity having the form of drops or bubbles. In the case of two-phase solvent system must first be removed from the internal phase.

In addition, as an alternative to the first of the above methods mentioned cavity can be formed by adding containing the polymer and the active substance solution of auxiliary substances, forming gas or gases, thereby foaming mass. It foaming through the gassing occurs during the receipt of the polymer mass, or application of the said mass to the substrate, or even during the subsequent drying process. Substance or mixture of substances applicable to gas, known to specialists in this field of technology.

Moreover, the foaming can also be carried out the change by expanding pre-dissolved gas.

Used gas is preferably an inert gas, such as nitrogen, carbon dioxide or helium or a mixture.

Alternatively, the manufacturer proposed in the present invention, the dosage forms can be started with a melt of the polymer or mixture of polymers of the matrix. While in principle it is easier to handle in comparison with the known from the prior art compositions for coatings applied from the melt.

In the above-mentioned polymer melt one of the above methods is injected gas or mixture of gases to cause foaming of the melt. Then the melt is applied onto an appropriate substrate or ekstragiruyut or poured into a mold, then cooled, i.e. allow to harden. Manufacturer of melt is unacceptable, if the active substance is unstable or volatile at the melting temperature of the polymer melt. Optionally, the polymer melt can be added excipients to reduce the melting point.

As a further improvement of the above-described manufacturing methods are first obtained a polymer matrix in the form of a block. Then, i.e. after drying or curing of the above-mentioned block cut out the desired lamellar dosage forms.

Proposed in the present invention the dosage form, the advantage is however applicable for administration of drugs in the oral or rectal, vaginal or intranasal. They can also be used as in the treatment of humans and in veterinary medicine.

Example 1

A brief description of the proposed in the present invention the dosage form

IngredientsContent (wt.%)
Kollicoat®IR67,50
Nicotinate17,90
The fragrance of peppermint11,75
Menthol2,55
Sucralose0,285
Blue pigment No. 10,015

Example 2

The manufacturer proposed in the present invention the dosage form

For manufacturing of the proposed invention the dosage form dissolved in water Kollicoat®IR (within 30 min with stirring, at room temperature) and introduced other additives. By setting to obtain a foamed material introduced air into the composition, which is then caused to the substrate and dried at a temperature of 80°C.

1. Plate form of delivery, dissolving or disintegrating in aq the th environment, to release at least one pharmaceutical or cosmetic active substance in a hole or cavity in the body, comprising a polymer matrix in the form of a hardened foam with spaces or cavities, and at least one pharmaceutical or cosmetic active substance, characterized in that the polymer matrix is a graft copolymer of polyvinyl alcohol and polyethylene glycol, consisting of 75% of polyvinyl alcohol and 25% peg.

2. Plate form of delivery according to claim 1, characterized in that the space or cavity in the matrix are isolated from each other and preferably are in the form of bubbles.

3. Plate form of delivery according to claim 1 or 2, characterized in that the said space or cavity filled with air or gas, preferably an inert gas, more preferably nitrogen, carbon dioxide, helium, a mixture of these gases, or a mixture of two of these gases.

4. Plate form of delivery according to any one of claims 1 to 3, characterized in that it is preferably in the form of lozenges, the thickness of the mentioned dosage form is preferably from 50 μm to 5 mm, particularly preferably from 0.5 to 1 mm.

5. A method of manufacturing a plate form of delivery according to any one of claims 1 to 4, characterized in that
a) receive a solution containing, what about the least one graft copolymer of polyvinyl alcohol and polyethylene glycol and at least one active substance;
b) churn the solution by introducing a gas or mixture of gases, or by chemical fumigation, or by increasing the dissolved gas is not necessary after prior addition of a foam stabilizer;
C) put the foam solution on a substrate and
g) give caused the solution to harden by drying and removal of solvent.

6. A method of manufacturing a plate form of delivery according to any one of claims 1 to 4, characterized in that
a) receive containing polymer melt (hot melt)containing at least one graft copolymer of polyvinyl alcohol and polyethylene glycol, and at least one active substance;
b) churn the melt by introducing a gas or mixture of gases, or by chemical fumigation, or by increasing the dissolved gas is not necessary after prior addition of a foam stabilizer;
C) is obtained from the above-mentioned melt polymer matrix in the form of block;
g) cutting the solidified block to get the product plate.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, and concerns a pharmaceutical oral formulation for nicotine or its derivative delivery to a subject by means of oral mucosa absorption, containing nicotine where the above-stated oral formulation is buffered with at least tromethanole.

EFFECT: what is presented is the method of oral nicotine delivery for reduction of craving to smoke or use tobacco, and also the methods for preparing the oral formulation, applying the oral formulation for nicotine uptake in the subject's mouth and applying nicotine for making the oral formulation for treating tobacco or nicotine dependence.

57 cl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, particularly a water-soluble film which disintegrates in a mouth for active agent delivery. The disintegrating film contains at least one water-soluble polymer and one active agent. The present invention also offers methods for making the disintegrating oral film and applying the disintegrating film for oral of an effective dose of the active agent for absorption through an oral mucosa. According to certain versions, the disintegrating film contains at least one water-soluble polymer and one active nicotine.

EFFECT: making the water-soluble film which disintegrates in the mouth for the active agent delivery.

7 cl, 10 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a chewing gum containing (a) an interior which contains a first flavouring agent which is mint; (b) at least one active pharmaceutical ingredient (API) in the interior and/or in one or more coatings; (c) at least one internal polymer film coating of the interior containing at least one second flavouring agent selected from a group consisting of citrus, cinnamon, berries or mixed fruit; and (d) at least one external solid coating of the latter internal polymer film coating. The preferential API is nicotine.

EFFECT: invention provides a prolonged effect of the flavouring agents, predominance of the flavouring agents in the coating in the interior, avoidance of problems of chemical or pharmaceutical incompatibility of the medicine in the interior and the flavouring agents in the coatings, and higher control of medicine release.

19 cl, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and its application for prevention and treatment of abuse with psychoactive substances and dependence on psychoactive substances, which contains compound of formula (R)-2-{3-[1-(acenaphthene-1-yl)pyperidin-4-yl]-2,3-dihydro-2-oxo-benzimidazol-1-yl} -N-methyl acetamide or its pharmaceutically acceptable salt as active ingredient.

EFFECT: compound, which is agonist and has highly selective affinity to ORL-1 receptors, possesses effects of reduction of intensity of alcohol abstinence symptoms and suppression of surplus intake of alcohol and other psychoactive substances.

18 cl, 1 tbl, 8 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to certain N-alkylcarbonylaminoacid esters of formula where R1 independently represents hydrogen or methyl; R2 independently represents alkyl C1-C2 and R3 independently represents alkyl C1-C4, offered in the present invention, as well as to compositions and therapies with using the declared compounds.

EFFECT: preparing new compounds which effect on sensory processes.

27 cl, 7 tbl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to development of a product reducing craving for smoking. The product represents a tablet (or sweet, or fruit pastille), containing powdered seeds of Hindu lotus (Nelumbo nucifera Gaertn), a dry extract of grape stems, sorbite (isomalt), aromatiser "Prunes", aromatiser "Hazelnut", sweetener aspartame, calcium stearate and aerosil.

EFFECT: product facilitates getting out of tobacco smoking, eliminates the accumulated hazardous substances from the body, exhibits an immediate positive effect, including in heavy smokers, with no severe distressful getting out of the habit and excessive strength of will efforts.

4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to dosage forms containing an active amount of pharmacologically acceptable Buproprion salt - Bupropion Hydrobromide, as well as to the administration of such dosage forms in treating one or more conditions of patients wherein the administration of Bupropion or its pharmacologically acceptable salt is allowed.

EFFECT: Bupropion Hydrobromide dosage forms exhibit with higher stability in comparison with the dosage forms containing Bupropion Hydrochloride that is proven by smaller reduction of activity of the compositions when stored for 3 or 6 months minimum under the forced conditions at 40°C and relative humidity 75%.

81 cl, 69 dwg, 73 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: ,

where R1 is selected from a group consisting of cycloalkyl which is unsubstituted or substituted with hydroxy or lower alkoxy, lower hydroxylalkyl, lower hydroxyhalogenalkyl, -CH2-CR9R10-cycloalkyl; R9 is hydrogen or lower alkyl; R10 is hydrogen, hydroxy or lower alkoxy; R2 is hydrogen; X is O or NR14; R14 is hydrogen or lower alkyl; R3 is selected from a group consisting of lower alkyl, cycloalkyl, lower cycloalkylalkyl, lower alkoxyalkyl, lower halogenalkyl, lower carbamoylalkyl, lower phenylalkyl, lower heterocyclylalkyl, where the heterocyclyl is a saturated 4- or 5-member ring containing one or two oxygen atoms, lower heteroarylalkyl, where the heteroaryl group is unsubstituted or mono- or disubstituted with a halogen, and phenyl which is unsubstituted or mono- or disubstituted with a halogen; or R3 and R14 together with a nitrogen atom to which they are bonded form an N-heterocyclic ring selected from pyrrolidinyl, piperidinyl or azepanyl; R4 and R8 independently denote hydrogen or halogen; R5 and R7 are independently selected from a group consisting of hydrogen, halogen, lower halogenalkyl, lower halogen, alkoxy and cyano; R6 is selected from a group consisting of hydrogen, halogen, lower halogenalkyl, lower halogen alkoxy and cyano; and pharmaceutically acceptable salts thereof, as well as to a pharmaceutical composition based on said compounds, which has CB1 modulating activity.

EFFECT: novel compounds which can be used to treat and prevent diseases associated with modulation of CB1 receptors, such as obesity, are obtained and described.

23 cl, 153 ex

FIELD: food industry.

SUBSTANCE: method deals with production of a smokeless tobacco product (snus) and relates to tobacco industry. The method includes careful selection of tobacco raw material wherein one determines nicotine content by express method immediately after selection. The vegetal raw material is carefully selected and mixed with the selected tobacco raw material. The tobacco raw material and vegetal material mixture is milled, fractionated by way of screen sizing, one selecting the tobacco raw material fraction strained through a sieve with 1×1 mm size holes. Then one determines nicotine content in the mixture by express method. Then culinary salt water solution is prepared; one pours the solution on the selected fraction and carefully mixes it till a homogeneous mass production. The prepared homogeneous mass is maintained at room temperature during no more than 30 minutes; one measures pH level and adds an acidity regulator in a quantity sufficient for the extract pH to be 7.8 - 8.2. Then one performs pasteurisation by a conventional method and adds a softener to the mixture. One performs cooling and conditioning during one day. One forms smokeless tobacco product from the produced mixture, the product having been prepared in accordance with one of the proposed versions of the invention, and the product is packed by one of the conventional methods.

EFFECT: produced smokeless tobacco product satisfies human physiological need for nicotine; it has a specified taste and aroma, contains less toxic agents which reduces the risk of damage to the consumer's health.

4 cl, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of treating one or more drug dependences, nicotine addiction and/or obesity, involving administration of an effective amount of the compound, sufficient for lowering production and/or secretion of dopamine, where the said compound has general formula: and its pharmaceutically acceptable salts, where R1 is hydrogen or methyl when R2 is Cy; R2 is hydrogen or methyl when R1 is Cy; and where Cy is a group which is optionally substituted with -R, -OR, -NR2 or a halogen, where each R is independently optionally substituted with a lower alkyl, aryl or heteroaryl. The invention also relates to methods of treating one or more drug dependences, nicotine addiction or obesity.

EFFECT: novel methods of treating addictions.

5 cl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are offered a dalargin-containing intranasal composition suspended or dissolved in a liquid propellant, containing stabilising and suspending agents and/or cosolvents, and its application for treating the diseases (particularly, gastric ulcer, duodenal ulcer, pancreatitis, pancreatonecrosis).

EFFECT: it is shown that the intranasal composition provides good absorbability; due to optimum viscosity the composition is distributed over a surface of a nasal mucosa and kept there for a long time, as well as higher bioavailability and a prolonged therapeutic effect of the declared agent in comparison with traditional dalargin compositions.

6 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to transporting filler for introduction of biologically active compounds, which contains one or more C1-C4 alcohols, water and combination of one or more diphosphate derivatives of electronic transfer agents and one or more monophosphate derivatives of electronic transfer agents. C1-C4 alcohols are present in amount from 0.5 to 50% by weight. Preferably C1-C4 alcohol represents ethanol. Transporting filler can have the shape of vesicles.

EFFECT: transporting filler in accordance with invention increases bioavailability of biologically active compounds, in particular, pharmaceutical preparations, including cosmetic ones.

33 cl, 4 dwg, 1 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: method of producing small-size (no more than 400 nm) liposomes containing INH included in liposomes in the maximally high concentration differs by the fact that there is prepared an isoniaside solution of the concentration 10-95 mg/ml in an aqueous medium; a surface of the prepared solution is coated with a layered powder of mixed lipids consisting of glycosphingolipids and phospholipids, and the powder is dispersed in weak mixing; then the dispersion is incubated at temperature 55-80°C for 10-20 minutes; the prepared liposomes are separated from INH by a gel filtration method.

EFFECT: method improvement.

7 cl, 2 dwg, 1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: treatment of chronic gonorrheal and gonorrheal-bacterial urethritis is ensured by antibiotic therapy and local treatment of clarithromycin in a liposomal form in the concentration 0.015 mg/ml, temperature 24-28°C. A length of procedure is 10-15 minutes. The therapeutic course is 5-7 days.

EFFECT: prevented recurrent disease, reduced side effects and complications due to localisation of antibacterial, antiinflammatory and phagocytosis stimulating action of clarithromycin by its delivery into a cell phagocyting Ngonorrhoeae and Saureus with higher antibiotic resistance.

2 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: invention relates to pharmaceutical compositions for inhalation introduction, containing water solution of fluorochinolone antimicrobial medication, preferably levofloxacin or ofloxacin, and bivalent or trivalent cation. Cation is selected from calcium, aluminium, zinc and iron. Compositions also can contain other antimicrobial medication and sweetener. Invention also relates to methods of treating lung infection, chronic obstructive lung disease or cystic fibrosis by introduction of said compositions to patient, who needs it. Invention also describes sets and systems for introduction, including container with composition by invention and sprayer.

EFFECT: medication in high concentration is delivered directly to affected tissue for treatment of bacterial infection in animals and people.

122 cl, 53 dwg, 37 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: medication for photodynamic therapy (PDT) includes photosensitising substance based on hydrophilic chlorine E6 derivative, phosphatidylcholine, cholesterol, citric acid and saccharose with definite molar component ratio. Method of obtaining said medication includes dissolution of phosphatidylcholine and cholesterol in chloroform, mixing said solutions and further evaporation under vacuum until formation of film, which is dispersed with water solution of chlorine E6 derivative into liposomal dispersion. After that, into liposomal dispersion water solution of saccharose and citric acid with pH 5.0 is added and lyophilised, and immediately before intravenous introduction redispersed with application of distilled water or physiological solution. Method of carrying out PDT lies in systemic introduction of claimed medication and irradiation of pathologic section 4-5 hours after its introduction with optic irradiation, absorbed by chlorine E6. Claimed method of obtaining medication for PDT ensured increase of chlorine E6 derivative inclusion into said medication, increase of its stability in long storage and increase of its technological output.

EFFECT: high efficiency of photodynamic therapy and selectiveness of accumulation.

3 cl, 4 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to saturated monophase solutions of medication in mixture of solvent and propellent together with film-generating preparation, which when introduced locally possess values of transdermal diffusion flow, exceeding values predicted by Fick's law. Pharmaceutic medication is present in composition at saturation value, of at least, 80%, film-generating preparation represents polymer, in amount from 0.1 to 40 % wt/wt.

EFFECT: increase of composition efficiency.

26 cl, 19 ex, 23 tbl, 14 dwg

FIELD: medicine.

SUBSTANCE: as an active substance, an aerosol contains aprotinin taken in the amount 23 to 30 mg in 100 ml of the preparation; a propellant is 1,1,1,2-tetrafluoroethane 70-84 vol. %; the solvents are ethanol 8-15 vol. %, glycerine 5-10 vol. %, water and a stabiliser is peppermint oil. The aerosol is pressurised in an aerosol container with a measuring valve.

EFFECT: preparation under the invention preserves native use and long storage antiprotease and antiviral properties of aprotinin.

6 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular for treatment of psoriasis. Medication for treatment of psoriasis, which contains solution of phospholipids in 70% ethyl alcohol and water solution of sodium deoxyribonucleate, components being taken in specified ratio.

EFFECT: medication is efficient for treatment of psoriasis.

4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: in claimed invention it suggested are liposome compositions, which contain substituted ammonia and/or polyanion and, optionally, desirable therapeutic agent or expressing contrast substance.

EFFECT: invention provides efficient method of obtaining liposome compositions.

141 cl, 40 tbl, 74 ex, 47 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, and concerns a pharmaceutical oral formulation for nicotine or its derivative delivery to a subject by means of oral mucosa absorption, containing nicotine where the above-stated oral formulation is buffered with at least tromethanole.

EFFECT: what is presented is the method of oral nicotine delivery for reduction of craving to smoke or use tobacco, and also the methods for preparing the oral formulation, applying the oral formulation for nicotine uptake in the subject's mouth and applying nicotine for making the oral formulation for treating tobacco or nicotine dependence.

57 cl, 10 ex

Up!